A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy

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http://hdl.handle.net/10138/205634

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Chew , T , Haase , B , Bathgate , R , Willet , C E , Kaukonen , M K , Mascord , L J , Lohi , H T & Wade , C M 2017 , ' A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy ' , G3 - Genes genomes genetics , vol. 7 , no. 7 , pp. 2327-2335 . https://doi.org/10.1534/g3.117.043109

Title: A Coding Variant in the Gene Bardet-Biedl Syndrome 4 (BBS4) Is Associated with a Novel Form of Canine Progressive Retinal Atrophy
Author: Chew, Tracy; Haase, Bianca; Bathgate, Roslyn; Willet, Cali E.; Kaukonen, Maria K.; Mascord, Lisa J.; Lohi, Hannes T.; Wade, Claire M.
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, University of Helsinki
Date: 2017-07
Language: eng
Number of pages: 9
Belongs to series: G3 - Genes genomes genetics
ISSN: 2160-1836
URI: http://hdl.handle.net/10138/205634
Abstract: Progressive retinal atrophy is a common cause of blindness in the dog and affects >100 breeds. It is characterized by gradual vision loss that occurs due to the degeneration of photoreceptor cells in the retina. Similar to the human counterpart retinitis pigmentosa, the canine disorder is clinically and genetically heterogeneous and the underlying cause remains unknown for many cases. We use a positional candidate gene approach to identify putative variants in the Hungarian Puli breed using genotyping data of 14 family-based samples (CanineHD BeadChip array, Illumina) and whole-genome sequencing data of two proband and two parental samples (Illumina HiSeq 2000). A single nonsense SNP in exon 2 of BBS4 (c.58A > T, p.Lys20*) was identified following filtering of high quality variants. This allele is highly associated (P-CHISQ = 3.425e(-14), n = 103) and segregates perfectly with progressive retinal atrophy in the Hungarian Puli. In humans, BBS4 is known to cause Bardet-Biedl syndrome which includes a retinitis pigmentosa phenotype. From the observed coding change we expect that no functional BBS4 can be produced in the affected dogs. We identified canine phenotypes comparable with Bbs4-null mice including obesity and spermatozoa flagella defects. Knockout mice fail to form spermatozoa flagella. In the affected Hungarian Puli spermatozoa flagella are present, however a large proportion of sperm are morphologically abnormal and
Subject: Hungarian Puli
whole-genome sequencing
blindness
obesity
infertility
GENOME-WIDE ASSOCIATION
ROD-CONE DEGENERATION
DNA-SEQUENCING DATA
RETINITIS-PIGMENTOSA
DOG BREEDS
PRIMARY CILIUM
DOMESTIC DOG
MUTATION
THERAPY
MODEL
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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